Genetic determinants of Graves disease

Basedow-Graves disease is an autoimmune thyroid syndrome. Genetic factors contribute to the pathogenesis of Graves disease, and current findings confirm that a number of genes may be involved in the development of autoimmune thyrotoxicosis. At present three loci, namely human leukocyte antigen (HLA, 6p21.3), cytotoxic T-lymphocyte-associated esterase-4 (CTLA4, 2q33), and thyroid-stimulating hormone receptor (TSHR, 14q31), are the only well-known genetic determinants for Graves disease. It is difficult to determine clearly the contribution of large multifunctional proteasome genes and transporter genes associated with antigen processing in the disorder, because of strong linkage disequilibrium between these genes and certain HLA alleles. Two recently discovered suspectibility loci, 20q11.2 and Xq21.33-q22, should be studied to find specific genes linked to Graves disease.